Restriction of memory B cell differentiation at the germinal center B cell positive selection stage

Autor/innen

  • A. Toboso-Navasa
  • A. Gunawan
  • G. Morlino
  • R. Nakagawa
  • A. Taddei
  • D. Damry
  • Y. Patel
  • P. Chakravarty
  • M. Janz
  • G. Kassiotis
  • R. Brink
  • M. Eilers
  • D.P. Calado

Journal

  • Journal of Experimental Medicine

Quellenangabe

  • J Exp Med 217 (7): e20191933

Zusammenfassung

  • Memory B cells (MBCs) are key for protection from reinfection. However, it is mechanistically unclear how germinal center (GC) B cells differentiate into MBCs. MYC is transiently induced in cells fated for GC expansion and plasma cell (PC) formation, so-called positively selected GC B cells. We found that these cells coexpressed MYC and MIZ1 (MYC-interacting zinc-finger protein 1 [ZBTB17]). MYC and MIZ1 are transcriptional activators; however, they form a transcriptional repressor complex that represses MIZ1 target genes. Mice lacking MYC-MIZ1 complexes displayed impaired cell cycle entry of positively selected GC B cells and reduced GC B cell expansion and PC formation. Notably, absence of MYC-MIZ1 complexes in positively selected GC B cells led to a gene expression profile alike that of MBCs and increased MBC differentiation. Thus, at the GC positive selection stage, MYC-MIZ1 complexes are required for effective GC expansion and PC formation and to restrict MBC differentiation. We propose that MYC and MIZ1 form a module that regulates GC B cell fate.


DOI

doi:10.1084/jem.20191933